Microarrays of nucleic acids are used to detect nucleic acid molecules in a sample. The microarray consists of different nucleic acid molecules (referred to as the “probe nucleic acids”) that are immobilized on a solid support (sometimes referred to as a “chip”). Each nucleic acid probe is immobilized on the chip at a known location. A sample, possibly containing nucleic acid sequences (referred to as “target nucleic acids”), is then presented to the probe nucleic acid molecules immobilized on the chip. Complementary binding of a target nucleic acid in the sample to a probe nucleic acid molecule on the chip generates a detectable signal, for example a fluorescent signal. The intensity of the detectable signal is proportional, or at least indicative, of the abundance of the target nucleic acid in the sample. A large number (typically over 1,000) of probe nucleotide sequences may be immobilized on the chip, so that an equally large number of target sequences in the sample, may be detected simultaneously using a single chip.
Microarray techniques have been used to compare gene expression levels in different tissues, or for comparing expression levels in healthy and diseased tissue of the same type. The level of gene expression in a given tissue provides a signature of the tissue. Similarly, the level of gene expression in a diseased tissue provides a signature of the disease.
In principle, the signature of gene expression in a tissue can be used to diagnose a disease in the tissue. For example, it is known that the various forms of leukemia are distinguishable by their characteristic pattern of gene expression. For this, the level of gene expression in the tissue is determined in the individual and compared with that previously obtained from an individual having the disease and from a healthy individual. In practice, however, the diagnosis is complicated by variability in the gene expression in the tissue type in different healthy individuals and in different individuals having the disease as well as the similarity of the gene expression level in the same tissue in different, but related diseases, such as various forms of leukemia.